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- Anand, Kanwlajeet J. S., et al.
(författare)
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Assessment of continuous pain in newborns admitted to NICUs in 18 European countries
- 2017
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Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 106:8, s. 1248-1259
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Continuous pain occurs routinely, even after invasive procedures, or inflammation and surgery, but clinical practices associated with assessments of continuous pain remain unknown.Methods: A prospective cohort study in 243 Neonatal Intensive Care Units (NICUs) from 18 European countries recorded frequency of pain assessments, use of mechanical ventilation, sedation, analgesia, or neuromuscular blockade for each neonate upto 28 days after NICU admission.Results: Only 2113/6648 (31·8%) of neonates received assessments of continuous pain, occurring variably among tracheal ventilation (TrV, 46·0%), noninvasive ventilation (NiV, 35·0%), and no ventilation (NoV, 20·1%) groups (p<0·001). Daily assessments for continuous pain occurred in only 10·4% of all neonates (TrV: 14·0%, NiV: 10·7%, NoV: 7·6%; p<0·001). More frequent assessments of continuous pain occurred in NICUs with pain guidelines, nursing champions, and surgical admissions prompted (all p<0·01), and for newborns <32 weeks gestational age, those requiring ventilation, or opioids, sedatives-hypnotics, general anesthetics (O-SH-GA) (all p<0·001), or surgery (p=0·028). Use of O-SH-GA drugs increased the odds for pain assessment in the TrV (OR:1·60, p<0·001) and NiV groups (OR:1·40, p<0·001).Conclusion: Assessments of continuous pain occurred in less than one-third of NICU admissions, and daily in only 10% of neonates. NICU clinical practices should consider including routine assessments of continuous pain in newborns.
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| 2. |
- Maurer, Matthew, et al.
(författare)
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3-Phosphoinositide-dependent kinase 1 potentiates upstream lesions on the phosphatidylinositol 3-kinase pathway in breast carcinoma
- 2009
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Ingår i: Cancer Research. - 1538-7445. ; 69:15, s. 306-6299
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Tidskriftsartikel (refereegranskat)abstract
- Lesions of ERBB2, PTEN, and PIK3CA activate the phosphatidylinositol 3-kinase (PI3K) pathway during cancer development by increasing levels of phosphatidylinositol-3,4,5-triphosphate (PIP(3)). 3-Phosphoinositide-dependent kinase 1 (PDK1) is the first node of the PI3K signal output and is required for activation of AKT. PIP(3) recruits PDK1 and AKT to the cell membrane through interactions with their pleckstrin homology domains, allowing PDK1 to activate AKT by phosphorylating it at residue threonine-308. We show that total PDK1 protein and mRNA were overexpressed in a majority of human breast cancers and that 21% of tumors had five or more copies of the gene encoding PDK1, PDPK1. We found that increased PDPK1 copy number was associated with upstream pathway lesions (ERBB2 amplification, PTEN loss, or PIK3CA mutation), as well as patient survival. Examination of an independent set of breast cancers and tumor cell lines derived from multiple forms of human cancers also found increased PDK1 protein levels associated with such upstream pathway lesions. In human mammary cells, PDK1 enhanced the ability of upstream lesions to signal to AKT, stimulate cell growth and migration, and rendered cells more resistant to PDK1 and PI3K inhibition. After orthotopic transplantation, PDK1 overexpression was not oncogenic but dramatically enhanced the ability of ERBB2 to form tumors. Our studies argue that PDK1 overexpression and increased PDPK1 copy number are common occurrences in cancer that potentiate the oncogenic effect of upstream lesions on the PI3K pathway. Therefore, we conclude that alteration of PDK1 is a critical component of oncogenic PI3K signaling in breast cancer.
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